Intercalating agents with covalent bond forming capability. A novel type of potential anticancer agents. 2. Derivatives of chrysophanol and emodin

Abstract

Fifty-one new C-methyl-modified derivatives of the anthraquinones chrysophanol and emodin or their various methyl ethers were prepared for structure-activity relationship studies of anticancer activity against mouse leukemia L1210 and human leukemia HL-60 cells. Representative compounds were spectrophotometrically studied for their capacity to interact with natural and denatured DNA. In general, those anthraquinones bearing an amino function interact with DNA. 1,8-Dimethoxyanthraquinones are incapable of intercalating into DNA. 1- or 8-Monohydroxymono-methoxyanthraquinones, however, interact with DNA to some extent. No straightforward correlation is apparent between the DNA-affinity data of the compounds studied spectrophotometrically and their cytotoxic effects. Cytotoxic potencies of these compounds on cell growth inhibition during a 72-h period are inversely correlated to their potencies when inhibiting [3H]TdR incorporation into DNA during the initial 30 min of exposure. Surprisingly, some compounds that showed more cytotoxicity did not inhibit initial TdR incorporation (0-30 min), while some others that strongly inhibited TdR incorporation initially did not exhibit cytotoxicity in 72 h. The results suggest that the cytotoxicity produced by these compounds is time dependent and is not a direct result of initial inhibition of DNA replication.

Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies

“…iii. DNA intercalculating agents: Koyama et al (1989), Su et al (1995Su et al ( , 1999, Rastogi et al, (2002), Chang et al (2003). iv.…”

Regulation of cell proliferation, inflammatory cytokine production and calcium mobilization in primary human T lymphocytes by emodin from Polygonum hypoleucum Ohwi

“…We have identified it from P. hypoleucum Ohwi [2]. The biological activities of emodin include: (a) inhibition of envelope viral replication [34,35], (b) reduction of interleukin-1 (IL-1), IL-2, and IL-2 receptor expression in human mononuclear cells [36], (c) inhibition of protein tyrosine kinase activity [37 -39], (d) inhibition of adenosine 3¢-5¢-cyclic monophosphate (cAMP) phosphodiesterase (PDE) activity [40], (e) enhancement of the formation of Topo II-DNA cleavable complexes related to antitumor activity [41,42], (f) free radical scavenging activity [43], (g) modulation of Ca 2+ influx in skeletal muscle [44], and (h) inhibition of inflammation in rat liver tissue [45].…”

Bulbine-Knipholone, a New, Axially Chiral Phenylanthraquinone fromBulbine abyssinica (Asphodelaceae): Isolation, Structural Elucidation, Synthesis, and Antiplasmodial Activity

“…[1] A milk decoction of the roots is applied to cure body rash and sexually transmitted diseases, while related Bulbine species are used for the treatment of various ailments such as bacterial and fungal infections, eczema, venereal diseases, and rheumatism. [2] Previous chemical investigations on the genus Bulbine have resulted in the isolation of antioxidant isofuranonaphthoquinones such as 1 (see Figure 1), [3] DNA-intercalating [4] and antileukemic [5] anthraquinones such as chrysophanol (2) and aloe-emodin (3), [6] and axially chiral phenylanthraquinones with good antiplasmodial activities, [7] among them knipholone (4) [8,9] and isoknipholone (5). [10] These promising bioactivities and the importance of Bulbine plants in traditional medicine make the search for, and synthetic availability of, further metabolites rewarding goals.…”